The circulating and central endocannabinoid system in obesity and weight loss

Abstract

Introduction: In the past decade major advances have been made in the treatment of obesity, focused on restoring disturbances along the gut-brain axis. The endocannabinoid system (ECS) is a neuromodulatory signaling system, present along the entire gut-brain axis, that plays a critical role in the central and peripheral regulation of food intake and body weight. It is a promising treatment target for obesity, as several components of the ECS have been linked to body weight or food intake in humans. Evidence on the impact of weight loss on the ECS is more limited. Therefore, we set out to review the existing evidence for changes in central and circulating endocannabinoid levels after bariatric surgery and other weight loss strategies in humans. Methods: The PubMed, Embase and Web of Science databases were searched for relevant articles.Results: 56 human studies were identified that measured the circulating or central ECS in obesity or after a weight loss intervention. Most studies measuring circulating 2-AG found no difference between normal weight and obesity, or no correlation with BMI. In contrast, studies measuring circulating AEA in obesity found an increase or positive correlation with BMI. Two studies found a negative correlation between BMI and CB1 receptor availability in the brain. Only one study investigated the effect of pharmacological weight management on circulating endocannabinoid concentrations and found no effect on AEA concentrations. So far, six studies investigated potential changes in circulating endocannabinoids after bariatric surgery and reported conflicting results.Conclusion: The available evidence does not univocally support that circulating endocannabinoids are upregulated in people with obesity. There is a lack of studies investigating the involvement of the endocannabinoid system in weight loss. In addition, we identified several research needs which should be fulfilled to better understand the role of the ECS in obesity and its treatments.